【摘要】 设计并合成了聚谷氨酸-聚乙二醇@碳酸钙（PPG@CaCO₃）纳米遮蔽体系,用于遮蔽聚乙烯亚胺（PEI）。一方面,聚谷氨酸-聚乙二醇（PPG）可以降低PEI引起的细胞毒性,更有利于体内应用;另一方面,CaCO₃可有效改善PPG导致的转染效率下降,并在一定程度上提高PEI的细胞转染效率。对比遮蔽体系PPG@CaCO₃和聚谷氨酸-聚乙二醇@磷酸钙[PPG@Ca₃（PO₄）₂]发现,PPG@CaCO₃在微酸性环境中释放二氧化碳气体是提高细胞转染效率的关键因素。小鼠体内循环实验表明,PPG@CaCO₃遮蔽体系可以增加载体在血液中的循环时间。因此,PPG@CaCO₃遮蔽体系对于改善阳离子类基因载体的体内应用起到重要作用。更多还原

【Abstract】 Cationic polymers,especially polyethyleneimine（ PEI）,have received much attention in the field of non-viral vectors,for their better biological safety and high efficiency gene transfection. However,their higher positive charge density will produce greater cytotoxicity,and also,easily forming larger particles with protein,which limits their further usage in vivo. In this work,we designed a shielding system based on polyglutamic acid-polyethylene glycol @ calcium carbonate（ PPG @ CaCO₃） for shielding polyethyleneimine（ PEI）. On one hand,PGA-PEG（ PPG） can reduce the cytotoxicity caused by PEI,and is conducive to applied in vivo. On the other hand,CaCO₃ effectively offset the decreased transfection efficiency that caused by PPG,and even enhanced cell transfection efficiency of PEI. Compared with the polyglutamic acid-polyethylene glycol @ calcium phosphate[PPG@ Ca₃（ PO₄）₂],CaCO₃ releases carbon dioxide gas in acidic environment,which is a key factor to improve cell transfection efficiency. In vivo circulation experiments in mice show that the shielding system based on PPG@ CaCO₃ can effectively enhance long circulation. Therefore,the shielding system plays an important role in promoting the in vivo application of cationic gene vectors.更多还原